title: Tissue specific differentially methylated regions (TDMR): Changes in DNA methylation during development.
abstract: Tissue specific differentially methylated regions (TDMRs) were identified and localized in the mouse genome using second generation virtual RLGS (vRLGS). Sequenom MassARRAY quantitative methylation analysis was used to confirm and determine the fine structure of tissue specific differences in DNA methylation. TDMRs have a broad distribution of locations to intragenic and intergenic regions including both CpG islands, and non-CpG islands regions. Somewhat surprising, there is a strong bias for TDMR location in non-promoter intragenic regions. Although some TDMRs are within or close to repeat sequences, overall they are less frequently associated with repetitive elements than expected from a random distribution. Many TDMRs are methylated at early developmental stages, but unmethylated later, suggesting active or passive demethylation, or expansions of populations of cells with unmethylated TDMRs. This is notable during postnatal testis differentiation where many testis specific TDMRs become progressively "demethylated". These results suggest that methylation changes during development are dynamic, involve demethylation and methylation, and may occur at late stages of embryonic development or even postnatally.
authors.affiliation: Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Song
authors.forename: Saleh
authors.initials: S
authors.lastname: Mahmood
authors.forename: Srimoyee
authors.initials: S
authors.lastname: Ghosh
authors.forename: Ping
authors.initials: P
authors.lastname: Liang
authors.forename: Domminic J
authors.initials: DJ
authors.lastname: Smiraglia
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nagase
authors.forename: William A
authors.initials: WA
authors.lastname: Held
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods; D018899:CpG Islands; D019175:DNA Methylation; D004622:Embryo, Mammalian; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D016678:Genome; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D012984:Software; D013737:Testis / Q000378:metabolism; D014018:Tissue Distribution